Metastasis is the leading cause of mortality in colorectal cancer (CRC), the poorly understood process by which cancers spread in the body. Whilst metastasis is most-commonly studied by xenotransplantation of tumour cells into mice, zebrafish are gaining traction as an alternative model for such studies. The standard zebrafish xenotransplant assay exploits the inherent optical clarity and immune deficiency of zebrafish embryos that are less than 7 days old for transplantation of human cancer cells. Whilst ideal for imaging early metastatic event, the short window of immunodeficiency fails to capture later metastatic events such as colonization and secondary tumour formation. To overcome these limitations, we developed an immunodeficient Casper SCID Fli1: GFP zebrafish model that extends the window for tracking metastasis in zebrafish.
By supporting prolonged engraftment of human cancer cells, our new model allows us to track, at the single cell level, both the early and later steps of metastasis. Our recent analysis of a panel of colorectal cancer cell lines has allowed us to chart distinct propensities and modes of metastatic spread. Importantly, by extending the time frame available for tumour analysis, our new model also enables to test the impact of anti-cancer therapies in established tumour, which has not been possible to date. This extended zebrafish model thus provides a valuable platform for studying tumour biology and testing new anti-metastatic therapies in CRC and other cancers.